Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial
In brief
Doublet chemo with long-course radiotherapy lifts 3-year DFS to 75%
In a phase III trial of 458 high-risk rectal cancer patients, adding oxaliplatin-based doublet chemotherapy to long-course radiotherapy raised three-year disease-free survival from 66% to 75% and more than doubled pathologic complete response rates (26% vs 10%). Toxicity was higher during neoadjuvant treatment but overall severe adverse events and postoperative complications remained similar, supporting this intensified regimen as a new standard option.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 23 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Xin Wang, Yuanling Tang, Junyang Lu, Wenjian Meng, Ping Liu, Jitao Zhou, et al.
- PMID
- 42492015
- DOI
- 10.1200/JCO-25-03110
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 July 2026): Total neoadjuvant therapy with long‑course radiotherapy improves DFS in high‑risk
- Picked for Pathology and Forensic Medicine (top studies of the week, 26 July 2026).
- Picked for Surgery (paper of the day, 24 July 2026).
Abstract
PURPOSE: High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT). METHODS: In this multicenter, randomized, phase III trial, patients with stage II/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier: NCT03177382). RESULTS: Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8% v 66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929]; P = .016). Metastasis-free survival (MFS; 77.7% v 67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37% v 9.80%; P < .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03% v 6.19%; P = .943). Although grade ≥3 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59% v 8.56%; P < .001), severe toxicities during the entire treatment course (28.02% v 24.32%; P = .371) and major postoperative complications (3.98% v 2.94%; P = .567) were comparable. CONCLUSION: Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy‑based or nondoublet-concurrent TNT regimens.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.